Inclusion Criteria:
For clinical referral to screening visit:
- BMI >30 kg/m2 or >95th BMI-Percentile
- Weight Range of 75kg to 150kg
- Age 16 to <21 at baseline
- Elevated alanine aminotransferase (ALT) more than twice the upper limit of normal by gender (≥ 44 U/L for girls, ≥ 50 U/L for boys)63 within 3 months prior to screening (used for historic ALT value) OR diagnosis of NAFLD from ultrasound, MRI, or participants with biopsy-proven NASH within 12 months of screening.
- History of lifestyle modification to treat obesity or NAFLD.
- Tanner stage >2
- Normal fasting glucose (fasting blood glucose <100 mg/dL)
To be obtained at screening visit:
- Confirmation of obesity;
- Tanner stage 2,3,4 or 5;
- Normal fasting glucose tolerance (fasting blood glucose <100 mg/dL);
- If Screening ALT is used as inclusion criteria (if > 2x historic ALT value (historical value obtained clinically within 12 months of screening visit), repeated after 4 weeks \[unable to randomize until completed\]. If the repeat ALT is more than 50% increased or decreased over the screening ALT, a third ALT should be obtained. If a third ALT is not within 50% of the previous value, then the subject is ineligible but may be rescreened at a later date. If ALT is not used:
- An ultrasound will be done to diagnose NAFLD if the diagnosis has not previously been made by ultrasound, MRI or biopsy.
- A MRI-derived HFF ≥ 5.5%
- Willingness to adhere to lifestyle considerations throughout the study
Exclusion Criteria:
- ALT > 250U/L at screening
- History of significant alcohol intake or current use
- Impaired fasting glucose (>100 mg/dL)
- Diabetes (type 1 or 2)
- Current or recent (<6 months prior to enrollment) use of weight loss medication(s)
- Vitamin E supplementation or use of metformin
-washout period 30 days
- Previous bariatric surgery
- Prior use of empagliflozin
- Lower limb infection/ulceration within 3 months of screening
- Metal or magnetic implants, devices or objects inside of or on the body, which are not MRI compatible
- Structural and functional urogenital abnormalities, that predispose for urogenital infections
- Recent initiation (<3 months prior to enrollment) of anti-hypertensive or lipid medication(s)
- Major psychiatric disorder
- Known hypothalamic or pituitary dysfunction
- Current pregnancy or plans to become pregnant
- Females unwilling to be tested for pregnancy
- Females who are sexually active and not protects by an effective method of birth control (e.g. UID or medication or patch)
-can re-screen 30 days after getting on birth control
- Tobacco use
- Significant liver dysfunction (levels >5 times the upper limit of normal (ULN)):
- ALT (ULN = 50 U/L)
- AST (ULN = 48 U/L)
- GGT (ULN = 48 U/L)
- ALP (ULN = 115 U/L)
- Platelets < 150,000 cells/mm3
- Total bilirubin > 1.3 mg/dL
- INR > 1.3
- Albumin <3.2 g/dL
- Gilbert's Syndrome
- Any known causes of liver disease (except NAFLD and NASH)
- Significant renal dysfunction (estimated glomerular filtration rate \[eGFR\] < 80 mL/min/1.73 m2),
- Diagnosed monogenic obesity
- History of cancer
- Untreated thyroid disorder
- History of decompensation events (ascites, variceal bleeding, hepatic encephalopathy, or hepatocellular carcinoma)
- Current or recent (<6 months prior to enrollment) use of medication(s) associated with weight gain (e.g. atypical anti-psychotics).